- SHIKIMIC ACID-DERIVED COMPOUNDS FOR INHIBITION AND DETECTION OF AURORA A-ASSOCIATED TUMORS
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The present invention provides inventive compounds of formulae (I) and (II), pharmaceutically acceptable forms thereof, pharmaceutical compositions thereof, and methods for treatment and their use.
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Page/Page column 89
(2008/06/13)
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- Synthesis and preliminary evaluation of a library of polycyclic small molecules for use in chemical genetic assays
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(-)-Shikimic acid, 3, was converted into both enantiomers of epoxycyclohexenol carboxylic acid, 7, which were attached to a solid support via a photocleavable linker. Tandem acylation-1,3-dipolar cycloaddition with nitrones 11a-g yielded tetracyclic templates 12a-g. After development of several efficient coupling reactions of iodobenzyl tetracycles 12b-d and completion of extensive validation protocols, a splitpool synthesis yielded a binary encoded library calculated to contain 2.18 million polycyclic compounds. These compounds are compatible with miniaturized cell-based 'forward' chemical genetic assays designed to explore biological pathways and 'reverse' chemical genetic assays designed to explore protein function. As a simple illustration of the potential of these compounds, several were shown to activate a TGF-β-responsive reporter gene in mammalian cells.
- Tan, Derek S.,Foley, Michael A.,Stockwell, Brent R.,Shair, Matthew D.,Schreiber, Stuart L.
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p. 9073 - 9087
(2007/10/03)
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